Search

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and East Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions, and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Cross-tissue analyses indicated that over a third of effector genes most likely act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis, and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article.

Objective: There are no existing validated search filters for the group of 37 Organisation for Economic Co-operation and Development (OECD) countries. This study describes how information specialists from the United Kingdom’s National Institute for Health and Care Excellence (NICE) developed and evaluated novel OECD countries’ geographic search filters for MEDLINE and Embase (Ovid) to improve literature search effectiveness for evidence about OECD countries. Methods : We created the draft filters using an alternative approach to standard filter construction. They are composed entirely of geographic subject headings and are designed to retain OECD country evidence by excluding non-OECD country evidence using the NOT Boolean operator. To evaluate the draft filters’ effectiveness, we used MEDLINE and Embase literature searches for three NICE guidelines that retrieved >5,000 search results. A 10% sample of the excluded references was screened to check that OECD country evidence was not inadvertently excluded. Results : The draft MEDLINE filter reduced results for each NICE guideline by 9.5% to 12.9%. In Embase, search results were reduced by 10.7% to 14%. Of the sample references, 7 of 910 (0.8%) were excluded inadvertently. These references were from a guideline about looked-after minors that concerns both OECD and non-OECD countries. Conclusion: The draft filters look promising—they reduced search result volumes while retaining most OECD country evidence from MEDLINE and Embase. However, we advise caution when using them in topics about both non-OECD and OECD countries. We have created final versions of the search filters and will validate them in a future study.

We consider crack propagation in a crystalline material in terms of bifurcation analysis. We provide evidence that the stress intensity factor is a natural bifurcation parameter, and that the resulting bifurcation diagram is a periodic “snaking curve”. We then prove qualitative properties of the equilibria and convergence rates of finite-cell approximations to the “exact” bifurcation diagram.

Motivated by rate-independent stress-strain hysteresis observed in filled rubber, this article considers a scalar viscoelastic model in which the constitutive law is random and varies on a lengthscale which is small relative to the overall size of the solid. Using stochastic two-scale convergence as introduced by Bourgeat, Mikelic and Wright, we obtain the homogenized limit of the evolution, and demonstrate that under certain hypotheses, the homogenized model exhibits hysteretic behaviour which persists under asymptotically slow loading. These results are illustrated by means of numerical simulations in a particular one-dimensional instance of the model., 54 pages, 4 figures

The slip of glaciers over the underlying bed is the dominant mechanism governing the migration of ice from land into the oceans, contributing to sea-level rise. Yet glacier slip remains poorly understood or constrained by observations. Here we observe both frictional shear-stress and slip at the bed of an ice stream, using 100,000 repetitive stick-slip icequakes from Rutford Ice Stream, Antarctica. Basal shear-stresses and slip-rates vary from 10^4 to 10^7 Pa and 0.2 to 1.5 m day^(-1), respectively. Friction and slip vary temporally over the order of hours and spatially over 10s of meters, caused by corresponding variations in ice-bed interface material and effective-normal-stress. Our findings also suggest that the bed is substantially more complex than currently assumed in ice stream models and that basal effective-normal-stresses may be significantly higher than previously thought. The observations also provide previously unresolved constraint of the basal boundary conditions of ice dynamics models. This is critical for constraining the primary contribution of ice mass loss in Antarctica, and hence the endeavour to reduce uncertainty in sea-level rise projections.

The systematic development of Coarse-Grained (CG) models via the Mori-Zwanzig projector operator formalism requires the explicit description of several terms, including a deterministic drift term, a dissipative memory term and a random fluctuation term. In many applications, the memory and fluctuation terms are related by the fluctuation-dissipation relation and are, in general, more challenging to derive than the drift term. In this work we analyse an approximation of the memory term and propose a rational basis for a data-driven approach to an approximation of the memory and fluctuating terms which can be considered included in the class of the Markovian ones., 39 pages, 2 Figures

Objective: We previously developed draft MEDLINE and Embase (Ovid) geographic search filters for Organisation for Economic Co-operation and Development (OECD) countries to assess their feasibility for finding evidence about the countries. Here, we describe the validation of these search filters. Methods: We identified OECD country references from thirty National Institute for Health and Care Excellence (NICE) guidelines to generate gold standard sets for MEDLINE (n=2,065) and Embase (n=2,023). We validated the filters by calculating their recall against these sets. We then applied the filters to existing search strategies for three OECD-focused NICE guideline reviews (NG103 on flu vaccination, NG140 on abortion care, and NG146 on workplace health) to calculate the filters’ impact on the number needed to read (NNR) of the searches. Results: The filters both achieved 99.95% recall against the gold standard sets. Both filters achieved 100% recall for the three NICE guideline reviews. The MEDLINE filter reduced NNR from 256 to 232 for the NG103 review, from 38 to 27 for the NG140 review, and from 631 to 591 for the NG146 review. The Embase filter reduced NNR from 373 to 341 for the NG103 review, from 101 to 76 for the NG140 review, and from 989 to 925 for the NG146 review. Conclusion: The NICE OECD countries’ search filters are the first validated filters for the countries. They can save time for research topics about OECD countries by finding the majority of evidence about OECD countries while reducing search result volumes in comparison to no filter use.

Lattice defects in crystalline materials create long-range elastic fields which can be modelled on the atomistic scale using an infinite system of discrete nonlinear force balance equations. Starting with these equations, this work rigorously derives a novel far-field expansion of these fields. The expansion is computable and is expressed as a sum of continuum correctors and discrete multipole terms which decay with increasing algebraic rate as the order of the expansion increases. Truncating the expansion leaves a remainder describing the defect core structure, which is localised in the sense that it decays with an algebraic rate corresponding to the order at which the truncation occurred.

BACKGROUND The authors developed a validated geographic search filter to retrieve research about the United Kingdom (UK) from OVID Embase. It was created to be used alongside their previously published OVID MEDLINE UK filter in systematic literature searches for context-sensitive topics. OBJECTIVES To develop a validated geographic search filter to retrieve research about the UK from OVID Embase. METHODS The Embase UK filter was translated from the MEDLINE UK filter. A gold standard set of references was generated using the relative recall method. The set contained references to publications about the UK that had informed National Institute for Health and Care Excellence (NICE) guidance and it was used to validate the filter. Recall, precision and number-needed-to-read (NNR) were calculated using a case study. RESULTS The validated Embase UK filter demonstrated 99.8% recall against the references with UK identifiers in the gold standard set. In the case study, the Embase UK filter demonstrated 98.5% recall, 7.6% precision and a NNR of 13. CONCLUSION The Embase UK filter can be used alongside the MEDLINE UK filter. The filters have the potential to save time and associated resource costs when they are used for context-sensitive topics that require research about UK settings.

We show that Witt groups of spinor varieties (aka.\ maximal isotropic Grassmannians) can be presented by combinatorial objects called even shifted young diagram. Our method relies on the Blow-up setup of Balmer-Calm\`es, and we investigate the connecting homomorphism of the localization sequence via the projective bundle formula of Walter-Nenashev, the projection formula of Calm\`es-Hornbostel and the excess intersection formula of Fasel., Comment: An appendix by Heng Xie; Final version. Generalized to the case of general bundles with complete flags

Objectives Health apps are software programs that are designed to prevent, diagnose, monitor, or manage conditions. Inconsistent terminology for apps is used in research literature and bibliographic database subject headings. It can therefore be challenging to retrieve evidence about them in literature searches. Information specialists at the United Kingdom's National Institute for Health and Care Excellence (NICE) have developed novel validated search filters to retrieve evidence about apps from MEDLINE and Embase (Ovid). Methods A selection of medical informatics journals was hand searched to identify a “gold standard” (GS) set of references about apps. The GS set was divided into a development and validation set. The filters’ search terms were derived from and tested against the development set. An external development set containing app references from published NICE products was also used to inform the development of the filters. The filters were then validated using the validation set. Target recall was >90 percent. The filters’ overall recall, specificity, and precision were calculated using all the references identified from the hand search. Results Both filters achieved 98.6 percent recall against their validation sets. Overall, the MEDLINE filter had 98.8 percent recall, 71.3 percent specificity, and 22.6 percent precision. The Embase filter had 98.6 percent recall, 74.9 percent specificity, and 24.5 percent precision. Conclusions The NICE health apps search filters retrieve evidence about apps from MEDLINE and Embase with high recall. They can be applied to literature searches to retrieve evidence about the interventions by information professionals, researchers, and clinicians.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES The present work investigates the process of professionalization of Sergipe football in the light of the sociology of professions. It seeks to demonstrate the factors that build the professional field of football through two perspectives: first, attention to the relationship between state and sport; secondly, by the career study. The work has as a temporal frame based within three moments: the emergence of football in Sergipe, "professionalization" in 1960, and modernization starting in 2010. Therefore, it is divided into three stages. The first deals with the bibliographic review of the theoretical horizon of the research. The second consists of documentary research for analysis of the period between 1907 and 1960. The third stage is to conduct interviews with players in the under-20 category of the Associação Desportiva Confiança. The documentary review shows the relations between football and the state's agricultural elites in the state of Sergipe, revealing how internal conflicts in the sports field of football were associated with the disputes of influential local groups. Key figures in the construction of Sergipe's professional football participated in political conflicts at the same time. The interviews demonstrate how the codes and meanings produced within the sports field also directly influence their construction process. The Associação Desportiva Confiança incorporates and reproduces the new concepts that define a modern football, considering the physical structure of the club, training methods, new criteria for the selection of athletes, and incorporation of administrative methods. The research confirms that the construction of professional football in Sergipe takes place in an associated way, especially with: the state, local politics, and the economic sphere. Nevertheless, these external influences are not enough to describe its process. Professionalization also depends on the rules and codes internal to the field, as individuals consistently produce the meanings linked to the idea of "professional." Although the phenomenon of modernization is incipient in the Sergipe state, it is possible to demonstrate its influences and impacts through the Associação Desportiva Confiança. O presente trabalho investiga o processo de profissionalização do futebol sergipano à luz da sociologia das profissões. Busca demonstrar os fatores que constroem o campo profissional do futebol através de duas óticas: primeiramente, atenta-se para a relação entre Estado e esporte; em segundo lugar, utiliza o estudo de carreira. O trabalho tem como recorte temporal três momentos: o surgimento do futebol em Sergipe; a “legalização da profissionalização” em 1960, e a modernização a partir de 2010. Por isso, é dividido em três etapas. A primeira versa sobre o levantamento bibliográfico do horizonte teórico da pesquisa. O segundo constitui-se de pesquisa documental para investigação do período entre 1907-1960. A terceira etapa é a realização de entrevistas com jogadores da categoria sub-20 da Associação Desportiva Confiança. A pesquisa documental revela as relações entre o futebol sergipano e as elites agrárias do estado. Demonstra como os conflitos internos ao campo esportivo do futebol estavam associados às disputas das parentelas locais. Personagens fundamentais na construção do campo profissional do futebol em Sergipe estavam ligados aos conflitos políticos. As entrevistas demonstram como os códigos e sentidos produzidos dentro do campo esportivo também influenciam diretamente no seu processo de construção. A Associação Desportiva Confiança incorpora e reproduz os novos conceitos que definem um futebol moderno, considerando estrutura física do clube, métodos de treinamento, novos critérios de seleção de atletas, e incorporação de métodos administrativos. Os dados confirmam que o processo de construção do campo profissional futebolístico em Sergipe se dá de forma associada, sobretudo com: o Estado, a política local, e a esfera econômica. Apesar disso, essas influências externas ao campo não são suficientes para descrever seu processo de construção. A profissionalização depende também das regras e códigos internos ao campo, na medida que os indivíduos produzem constantemente os sentidos vinculados à ideia de “profissional”. Embora o fenômeno da modernização seja incipiente no estado, é possível demonstrar suas influências e impactos através da Associação Desportiva Confiança. São Cristóvão, SE

No abstract.

Background The National Institute for Health and Care Excellence's (NICE) United Kingdom (UK) geographic search filters for MEDLINE and Embase (OVID) retrieve evidence in literature searches for UK-focused research topics with high recall. Their precision and number-needed-to-read (NNR) was examined previously in case studies using a single review. This paper details a larger post-development study that was conducted to test the NICE UK filters' precision and NNR more extensively. Methods The filters' recall of included UK references from 100 reviews was calculated. As reproducible search strategies were not available for every review, the MEDLINE filter's precision and NNR were calculated using strategies from 25 reviews. Strategies from nine reviews were used for the Embase filter. Results The MEDLINE filter achieved an average of 96.4% recall for the included UK references from the 100 reviews and the Embase filter achieved an average of 97.4% recall. Compared to not using a filter, the MEDLINE filter achieved an average of 98.9% recall for the 25 reviews. Precision was increased by an average of 7.8 times, reducing the NNR from 357 to 46. The Embase filter achieved an average of 97.1% recall for the nine reviews. Precision was increased by an average of 5.1 times, reducing the NNR from 746 to 146. Conclusion There is more evidence to demonstrate that the NICE UK filters retrieve the majority of UK evidence from MEDLINE and Embase while increasing precision and reducing NNR. The filters can save time spent on selecting evidence for UK-focused research topics.

We formulate and study a stochastic model for the thermally-driven motion of interacting straight screw dislocations in a cylindrical domain with a convex polygonal cross-section. Motion is modelled as a Markov jump process, where waiting times for transitions from state to state are assumed to be exponentially distributed with rates expressed in terms of the potential energy barrier between the states. Assuming the energy of the system is described by a discrete lattice model, a precise asymptotic description of the energy barriers between states is obtained. Through scaling of the various physical constants, two dimensionless parameters are identified which govern the behaviour of the resulting stochastic evolution. In an asymptotic regime where these parameters remain fixed, the process is found to satisfy a Large Deviations Principle. A sufficiently explicit description of the corresponding rate functional is obtained such that the most probable path of the dislocation configuration may be described as the solution of Discrete Dislocation Dynamics with an explicit anisotropic mobility which depends on the underlying lattice structure., Comment: Major revision, including overhaul of notation, additions to Section 6 on Large Deviations, and resolution of conjecture in original version. 45 pages, 2 figures, 1 table